IADR Abstract Archives
Hyaluronan-fragments modify the transcriptional program of periodonto-pathogen-stimulated dendritic cells.
Objectives: Dendritic cells (DCs) are antigen-presenting cells involved in the initiation and regulation of the adaptive immune response. During periodontitis, immuno-inflammatory response and bone resorption are associated with the up-regulation of pro-inflammatory cytokines in stimulated DCs. In this context, periodontal bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, as well as damage-associated molecular patterns (DAMPs) released during periodontal tissue breakdown, such as low molecular weight hyaluronan (LMW-HA), have been proposed as potent inductors of host immune response by activating DCs. In this context, distinct DCs subsets with specific transcriptional programs have been described. Among them, IRF8/BATF3 cDC1 and IRF4/NOTCH2 cDC2 subsets have been associated with the etiopathogenesis of several inflammatory diseases. We hypothesized that LMW-HA up-regulates the expression of cDC1/cDC2-associated transcription factors in P. gingivalis or A. actinomycetemcomitans-stimulated DCs.
This study aimed to quantify and compare the expression levels of IRF8, BATF3, IRF4 and NOTCH2 in dendritic cells stimulated with P. gingivalis or A. actinomycetemcomitans, pulsed or not with LMW-HA.
Methods: Monocyte-derived DCs were obtained from healthy donors, pulsed at days 3 and 5 with 20 KDa-LMW-HA (100 µg/mL), and at day 7 stimulated with P. gingivalis or A. actinomycetemcomitans. Non-pulsed infected-DCs were used as control. Non-pulsed non-infected-DCs were used for comparison. The mRNA expression levels for BATF3, IRF4, IRF8 and NOTCH2 were quantified using qPCR.
Results: Higher expression levels of BATF3, IRF4 and NOTCH2 were detected in LMW-HA-pulsed A. actinomycetemcomitans-infected DCs as compared with non-pulsed infected-DCs. Higher expression levels of IRF4 and NOTCH2 were detected in LMW-HA-pulsed P. gingivalis-infected DCs as compared with non-pulsed infected-DCs.
Conclusions: LMW-HA induces an increment in the expression of transcription factors related with inflammatory DC subsets on infected-DCs.
This study aimed to quantify and compare the expression levels of IRF8, BATF3, IRF4 and NOTCH2 in dendritic cells stimulated with P. gingivalis or A. actinomycetemcomitans, pulsed or not with LMW-HA.
Methods: Monocyte-derived DCs were obtained from healthy donors, pulsed at days 3 and 5 with 20 KDa-LMW-HA (100 µg/mL), and at day 7 stimulated with P. gingivalis or A. actinomycetemcomitans. Non-pulsed infected-DCs were used as control. Non-pulsed non-infected-DCs were used for comparison. The mRNA expression levels for BATF3, IRF4, IRF8 and NOTCH2 were quantified using qPCR.
Results: Higher expression levels of BATF3, IRF4 and NOTCH2 were detected in LMW-HA-pulsed A. actinomycetemcomitans-infected DCs as compared with non-pulsed infected-DCs. Higher expression levels of IRF4 and NOTCH2 were detected in LMW-HA-pulsed P. gingivalis-infected DCs as compared with non-pulsed infected-DCs.
Conclusions: LMW-HA induces an increment in the expression of transcription factors related with inflammatory DC subsets on infected-DCs.